The introduction of biological agents in the treatment of systemic vasculitis offers the promise of targeted therapy with greater efficacy and fewer side effects than conventional treatments. In this paper, we review the rationale for biological strategies in vasculitis and discuss the results of clinical studies to date. The biotherapies discussed include immune-cell-depleting agents, both B- and T-cell targeted; costimulatory blockade; and cytokine blockade. Although most of these agents remain unproven until ongoing randomized clinical trials are complete, their introduction heralds a new era of vasculitis treatment and has provided novel insights into disease pathogenesis.